Influenza infection remains an important infection in animals and humans. Influenza is caused by viruses that undergo continuous antigenic changes/modifications and that possess an animal reservoir. Thus new epidemics and pandemics may occur in the future, and eradication of the disease will be difficult to achieve. Influenza viruses are well known in the art and described more in detail for example by P. Palese, Nature Medicine, vol. 10, no. 12, pp. S 82 to S 86 of December 2004, with further references. Briefly, the genome of the influenza A virus consists of eight single-stranded segments, and the viral particles has two major glycoproteins on its surface: hemagglutinin (H) and neuraminidase (N). With at least 15 different hemagglutinin (H1 to H15) and 9 different neuraminidase (N1 to N9) subtypes, there is a considerable antigenic variation among influenza viruses.
Influenza virus of type H5N1 Fowl Plague virus has been demonstrated to infect both pigs and man. The viruses can also be transmitted directly from avian species to humans (Claas et al., Lancet 1998, 351: 472; Suarez et al., J. Virol. 1998, 72: 6678; Subbarao et al., Science 1998, 279: 393; Shortridge, Vaccine 1999, 17 (Suppl. 1): S26-S29). Mortality in known human clinical cases approaches about 50%.
Over the last century pigs have been an important vector for influenza pandemics. Pigs, camels, and seals, preferably pigs, can serve as a ‘mixing chamber’ for avian influenza viruses, and therefore represent a potential risk factor for overcoming the species hurdles from poultry, the naturally reservoir of influenza viruses, to mammals. This normally occurs by double infections of the susceptible animals, e.g. pig, with both, an established mammalian (porcine), as well as an avian influenza virus. This double infection may create new recombinant viruses that may be the cause of human or porcine pandemics. Recent evidence would, however, indicate that a recombination of current avian H5 strains with mammalian influenza viruses will not result in highly virulent recombinants. On the other hand, avian influenza virus can infect pigs and by spontaneous mutations can become adapted to pigs. The critical hurdle will be overcome as soon as the virus can cause horizontal infections within a pig (or other mammalian) population.
Yet, a major part of Southeast Asian pigs have been infected with avian (H5) influenza virus strains originating from neighbouring poultry husbandry. As those infections have so far been sub-clinical, they can only be diagnosed by laboratory methods and thus are frequently overlooked. There is a high risk that those sub-clinically-infected pigs will serve as an opportunity for the virus to adapt to the mammalian system, spread within the porcine population, and also infect human beings.
As the species hurdle between pigs and humans is expected to be low the risk of horizontal infections of the variant ‘porcine’ influenza viruses within humans is dramatically increased. The currently available vaccines against influenza A infection are killed-virus vaccine preparations, that contain variants of the H1, H2 and H3 subtype of influenza. The use of those vaccines is limited to the vaccination of humans in order to prevent transmission from man to man. Thus those vaccines, including the current vaccination strategy to prevent man-to-man transmission, are not preventive with respect to the transmission and adaptation of non-mammalian influenza viruses to mammalians. Those vaccines, including the current vaccination strategy does not sufficiently consider the fact that non-mammalian influenza viruses, e.g. avian influenza viruses are able to infect non-human mammals, such as pigs, camels, seals, etc, and to recombine with mammalian influenza viruses in those non-human mammals.
Thus, there is a need to increase availability of new superior vaccines and new vaccination approaches to provide better approaches to control influenza infections and to have a positive impact on disease load.